- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02201329
Volasertib in Combination With Azacitidine in Japanese Patients With Myelodysplastic Syndrome or Chronic Myelomonocytic Leukemia
An Open Label Phase I Trial of Intravenous Volasertib in Combination With Subcutaneous Azacitidine in Japanese Patients With Higher-risk Myelodysplastic Syndrome or Chronic Myelomonocytic Leukemia
Study Overview
Status
Intervention / Treatment
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
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-
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Aichi, Nagoya, Japan
- Boehringer Ingelheim Investigational Site
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Gunma, Maebashi, Japan
- Boehringer Ingelheim Investigational Site
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Nagasaki, Nagasaki, Japan
- Boehringer Ingelheim Investigational Site
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Tokyo, Sinagawa-ku, Japan
- Boehringer Ingelheim Investigational Site
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion criteria:
- Patients of age >=20 and <=80 years
Patients with primary or treatment-related myelodysplastic syndrome (MDS) or chronic myelomonocytic leukemia (CMML), who are not eligible for hematopoietic stem cell transplantation based on the investigator's judgment, that meet one of the following criteria:
- Intermediate-2 and high-risk MDS according to the International Prognostic Scoring System, in the setting of 5-30% bone marrow blasts
- CMML with >= 10% marrow blasts without myeloproliferative disorder (white blood cell count of <13,000/ µL)
Patients with no prior azacitidine treatment, or with prior azacitidine treatment that meet one of the following criteria:
- Patients failing to achieve haematological improvement, partial remission, marrow complete remission or complete remission after 3 cycles of azacitidine or progressed at any time after start of azacitidine
- Patients achieved an initial response and subsequently develop disease progression or relapse
- Eastern Cooperative Oncology Group performance status score 0 or 1 at screening
- Signed written informed consent consistent with Good Clinical Practice.
Exclusion criteria:
- Treatment with systemic therapy for MDS, including an investigational drug, within 14 days before the first dose of study treatment, except for lenalidomide within 12 weeks before the first dose of study treatment, or lack of recovery from any acute toxicities pertinent to the prior systemic therapy.
- Prior treatment with volasertib
- Contraindications for azacitidine treatment according to the manufacturer's product information
- Known hypersensitivity to the trial drugs or its excipients
- Concomitant malignancy currently requiring active therapy (except for hormonal/anti-hormonal treatment, e.g. in prostate or breast cancer)
- QTcF prolongation >470 ms or QT prolongation deemed clinically relevant by the investigator (e.g., congenital long QT syndrome).
- Total bilirubin >1.5 x upper limit of normal (ULN) not related to Gilbert's syndrome, hemolysis, or secondary to MDS at screening
- Aspartate amino transferase or alanine amino transferase >2.5 x ULN
- Serum creatinine >1.5 x ULN at screening
- Arterial oxygen pressure <60 torr or arterial oxygen saturation <92% (at room air)
- Active hepatitis B or hepatitis C, or laboratory evidence of hepatitis with positive results of hepatitis B surface antigen and/or hepatitis C antibody.
- Human immunodeficiency virus infection.
- Severe illness or organ dysfunction involving the heart, lung, kidney, liver or other organ system, which in the opinion of the investigator would interfere with the evaluation of the safety of the study treatment including; infection requiring active treatment, poorly controlled ventricular/atrial tachyarrhythmia, use of heart pacer, unstable angina pectoris, history of myocardial infarction or severe congestive heart failure, clinically unstable cardiac or pulmonary disease
- Any significant concurrent psychiatric disorder or social situation that according to the investigator's judgment would compromise patient's safety or compliance, interfere with consent, study participation, or interpretation of study results
- All male patients and female patients of child bearing potential who are unwilling to use a medically acceptable method of contraception during the trial and at least 6 months after the end of study treatment (i.e. hormonal contraception, intrauterine device, condom with spermicide, etc.). Note: females are considered to be of child bearing potential unless they have been surgically sterilized or are post-menopausal (complete absence of menses for at least 12 months without other medical reasons).
- Pregnant or nursing female patients
- Known or suspected active alcohol or drug abuse
Study Plan
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: NA
- Interventional Model: SINGLE_GROUP
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: A
Volasertib escalating doses + azacitidine
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Azacitidine (subcutaneous)
Volasertib escalating doses (intravenous)
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of Participants With Dose Limiting Toxicities (DLTs) in the First Cycle for the Determination of the Maximum Tolerated Dose (MTD)
Time Frame: Up to 57 days.
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This outcome measure presents number of participants with DLTs in the first cycle for the determination of MTD. DLT was defined as any of the following Adverse Events (AEs) considered to be related to the study drug (Volasertib and/or Azacitidine).
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Up to 57 days.
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Maximum Tolerated Dose of Volasertib
Time Frame: Up to 57 days.
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This outcome measure presents MTD of Volasertib in Combination with Azacitidine.
The MTD was defined as the highest dose level at which Dose Limiting Toxicities (DLTs) were reported in not more than 1 in 6 evaluable patients during Cycle 1.
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Up to 57 days.
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Overall Objective Response (OR): Complete Remission (CR), Partial Remission (PR), or Marrow CR (mCR)
Time Frame: Up to 9 months.
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This outcome measure presents overall Objective Response (CR+PR+mCR).
Response to treatment was evaluated according to the International Working Group (IWG) 2006 criteria.
Best response was tabulated from all available data, with each patient being classified into one of the categories defined in CR, PR, mCR.
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Up to 9 months.
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Maximum Measured Concentration of the Volasertib 200 mg in Plasma (Cmax)
Time Frame: -0.05 hours before drug administration and 0:30 (hours:minutes), 1:00, 1:30, 2:00, 3:00, 4:00, 24:30, 48:30, 96:30, 144:30 and 335:55 after drug administration.
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This outcome measure presents maximum measured concentration of Volasertib 200 mg in plasma (Cmax).
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-0.05 hours before drug administration and 0:30 (hours:minutes), 1:00, 1:30, 2:00, 3:00, 4:00, 24:30, 48:30, 96:30, 144:30 and 335:55 after drug administration.
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Area Under the Concentration-Time Curve of Volasertib 200 mg in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞)
Time Frame: -0.05 hours before drug administration and 0:30 (hours:minutes), 1:00, 1:30, 2:00, 3:00, 4:00, 24:30, 48:30, 96:30, 144:30 and 335:55 after drug administration.
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This outcome measure presents area under the concentration-time curve of Volasertib 200 mg + Azacitidine 75 mg/m^2 in plasma over the time interval from 0 extrapolated to infinity (AUC0-∞).
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-0.05 hours before drug administration and 0:30 (hours:minutes), 1:00, 1:30, 2:00, 3:00, 4:00, 24:30, 48:30, 96:30, 144:30 and 335:55 after drug administration.
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Collaborators and Investigators
Sponsor
Publications and helpful links
Helpful Links
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Pathologic Processes
- Neoplasms by Histologic Type
- Neoplasms
- Disease
- Bone Marrow Diseases
- Hematologic Diseases
- Precancerous Conditions
- Myelodysplastic-Myeloproliferative Diseases
- Leukemia, Myeloid
- Syndrome
- Myelodysplastic Syndromes
- Leukemia
- Preleukemia
- Leukemia, Myelomonocytic, Chronic
- Leukemia, Myelomonocytic, Juvenile
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antimetabolites, Antineoplastic
- Antimetabolites
- Antineoplastic Agents
- Azacitidine
Other Study ID Numbers
- 1230.35
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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